AUCTORES
Globalize your Research
Case-Report | DOI: https://doi.org/10.31579/2690-8808/022
*Corresponding Author: Maneesh Gaddam, Pulmonary Fellow Division of Pulmonary and Critical Care Medicine BronxCare Health System 1650 Grand Concourse, Bronx, NY 10457 Affiliated with Icahn School of Medicine at Mount Sinai,
Citation: Maneesh Gaddam., Olga A. Reyes., Cosmina Zeana., Gilda D. Fuentes, (2020) Still’s disease mimicking sepsis in a young woman. A case report and literature review. J Clinical Case Reports and Studies, 1(6): Doi: 10.31579/2690-8808/022
Copyright: © 2020 Maneesh Gaddam, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 11 October 2020 | Accepted: 02 November 2020 | Published: 09 November 2020
Keywords: adult onset Still’s disease; polyarteritis nodosa; macrophage activation syndrome
Background
Adult onset Still’s disease (ASD) is a rare systemic auto-inflammatory condition that often poses a diagnostic dilemma due to nonspecific clinical signs and symptoms. We report a case of ASD that dramatically improved after a short course of steroids.
Case presentation
A 23-year-old women from Ghana presented with a two-week history of fever, sore throat, right-sided neck swelling and an evanescent, pruritic rash on her extremities. On exam she was febrile to 103 F, tachycardic, tachypneic, had tender, right-sided cervical lymphadenopathy, and diffuse joint tenderness with decreased range of motion. She was admitted to the ICU for possible sepsis and started on broad-spectrum antibiotics. Extensive work-up for possible infectious and auto-immune etiologies, including a bone marrow biopsy was negative. The diagnosis of Still’s disease was made based on the Yamaguchi criteria. The patient was started on methyl-prednisolone and significantly improved within 24 hours.
Conclusion
Patients presenting with ASD often represent a diagnostic challenge. Clinicians should be aware of this rare disorder, exclude other more frequent diseases and start early anti-inflammatory therapy to avoid poor outcomes.
Abbreviations
ASD: Adult Still’s disease
CRP: C-reactive protein
ESR: Erythrocyte sedimentation rate
HLH: Hemophagocytic lymphohistiocytosis
MAS: Macrophage activation syndrome
NSAIDS: Nonsteroidal anti-inflammatory drugs.
PAN: Polyarteritis nodosa
Adult Still’s disease (ASD) is a rare systemic auto inflammatory condition first described in children by Dr. George Still in 1896 as an entity similar to adult rheumatoid arthritis with associated splenomegaly and lymphadenopathy.[1] A similar condition with an evanescent maculopapular rash associated with fever usually in the evening, arthritis mainly affecting the knees, fingers, and wrists was later described by Bywaters. Associated features included splenomegaly, pleural effusions, and pericarditis.[2]
The exact incidence and prevalence of adult onset Still’s disease is unclear. Multiple studies suggest a higher incidence in women usually older than 35 years/age. A retrospective study of 62 cases in West France from 1982-1991, reported a disease incidence calculated over five years of 0.16/100,000. The mean age was 36 years, with two peaks of distribution at 15-25 and 36-45 years.[3] Other studies reported an estimated annual incidence of 0.4-0.62/100,000 adults and a prevalence of 3.4-6.77/100,000.[4,5] We present a young patient with features of sepsis which was subsequently diagnosed with ASD.
A 23-year-old female from Ghana with no past medical history or toxic habits was admitted to the intensive care unit with fever, tachycardia, and leukocytosis. The initial diagnosis was sepsis and she was started on broad-spectrum antibiotics. The patient has been living in the United States for the past 3 years after moving from Ghana, but she traveled to Kansas about 1 month prior to the presentation where she had unprotected sexual encounter with one partner. Patient reported painful right sided neck swelling of two weeks duration.
Soft tissue ultrasound of the neck revealed multiple right-sided lymph nodes, the largest measuring 1.2 x 0.8 x 1.0 cm in size. Initially, she was given non-steroidal anti-inflammatory (NSAIDS) medications and sent home. She returned to the hospital within 24 hours with pruritic erythematous rashes of upper and lower extremities, severe persistent neck swelling and pain associated with high fever and sore throat which prompted intensive care admission for possible sepsis. On exam, she was tachycardic with a heart rate of 140/min, febrile with a temperature of 102 °F, tachypneic with a respiratory rate of 25/ min and normotensive. There were tender right neck lymphadenopathy and bilateral tonsillar erythema, no stridor. Lungs were clear, no heart murmur, and no visceromegaly in the abdominal exam. Diffuse joint tenderness with a range of motion but no swelling or fluid was seen. Neurological and skin exam was normal. Computed tomogram of the neck only revealed small
right-sided lymphadenopathy. Chest-X-ray, electrocardiogram, echocardiogram, abdominal ultrasound, urine toxicology, HIV test, blood and urine cultures, chlamydia, gonorrhea, and syphilis testing, as well as hepatitis A, B and C were all negative. Rheumatoid factor was slightly positive (16.4 IU/mL), aldolase (28.9 U/L), ferritin (>5,000 ng/ml) and serum lactic dehydrogenase (658 unit/L) were elevated. Malaria smear in three consecutive days was negative. Autoimmune workup revealed negative anti-SCL 70, antinuclear, anti-CCP and anti-centromere antibodies. Serology revealed history of exposure to Epstein Barr and Cytomegaloviruses, negative Parvovirus B19 IgM and IgG antibodies. Serology for Dengue, Chikungunya, Zika, Leptospira and Lyme’s disease was negative. Pertinent laboratory during admission can be seen in Table 1.
Patient’s condition continued to deteriorate despite fluids and broadspectrum antibiotics including Piperacillin-Tazobactam, Vancomycin, Doxycycline. She was weak, febrile, tachycardic, and unable to move due to arthralgias and myalgias. Other differentials considered were adult Still’s disease, leukemia and lymphoma. Bone marrow biopsy was performed on day 6 of admission and patient was started on methylprednisolone; within 24 hours she became afebrile with resolution of tachycardia and tachypnea. She had a steady clinical recovery and within 3-4 days she was close to normal. Bone marrow biopsy reported a normocellular marrow with 70
The clinical presentation of ASD is non-specific; the triad of fever, evanescent rash and arthralgia/arthritis is the commonest presentation. Fever is seen in nearly 100% of patients, with the temperature being greater than 39°C. One study of 45 patients with ASD showed that only 43% of patients presented with the typical triad; fever was present in all patients, arthralgias in 98% and rash in 82% of the patients.[6] Physical exam is equally nonspecific. Another study with 62 patients, reported higher frequencies of sore throat (92%), weight loss (76%), lymphadenopathy (74%), pleuritis (53%), pneumonitis (27%), abdominal pain (48%), hepatomegaly (44%) or abnormal liver function tests (76%)”. Liver failure occurred in conjunction with the use of aspirin and NSAID use.[7] An elevated erythrocyte sedimentation rate (ESR) (100%) and leukocytosis (93.8%) were findings identified in a Thai study of ASD.[08]
In 1992, the Yamaguchi criterion was structured to improved identification and diagnosis of ASD. This criterion carries a sensitivity of 93.5%.[09] There are four major criteria which include high fever (39°C), rash (evanescent salmon-pink colored, which generally appear in association with fever), arthralgia/arthritis and leukocytosis. Minor criteria are sore throat, lymphadenopathy, hepatomegaly and/or splenomegaly, elevated liver function enzymes and negative rheumatoid factor and anti-nuclear antibody.[10] The patient should meet at least 5 of the above-mentioned criteria, out of which 2 must be major for the diagnosis of ASD to be considered. There is no specific test to confirm the diagnosis of ASD, which represent a challenge to the clinicians as many features of ASD can be seen in other more common conditions like sepsis, systemic inflammatory response syndrome, autoimmune disorders, hemophagocytic lymphohistiocytosis (HLH) and malignancy. Acute phase reactants such as ferritin, ESR, Creactive protein (CRP) will be elevated; a ferritin levels greater than 3,000 ng/mL can be observed and if levels are greater than 10,000 ng/mL, presence of co-existing HLH should be evaluated.[11] In cases where bone marrow biopsy is available, presence of peripheral neutrophilia, granulocyte hyperplasia and hypercellularity can be seen which helps to differentiate from the pancytopenia characteristic of hemophagocytic syndrome. Infectious etiologies to be consider includes viral hepatitis, acute HIV infection, parvovirus B19, mosquito-borne viral infections (such as Zika and Chikungunya viruses), Epstein-Barr, Cytomegalovirus, coxsackie virus, mumps, rubella, Lyme’s disease. Serology is helpful to exclude some of these diagnoses. Rheumatologic conditions such as rheumatoid arthritis, systemic lupus erythematosus, and reactive arthritis all have similar presentation; serology will help to narrow down diagnosis as the ANA, RF, anti-CCP negative and anti-dsDNA will be negative in ASD. Among the vasculitis disorders, polyarteritis nodosa (PAN) has the most similarities; however, the rash seen in PAN is purpuric with ulcerative lesions. Autoimmune serology, biopsy of an affected organ and vascular imaging studies can be useful for diagnosis. In cases where lymphomas and leukemias are been considered, peripheral smear and bone marrow biopsy will be helpful. An important hematologic entity to be considered is hemophagocytic lymphohistiocytosis (HLH); also known as macrophage activation syndrome (MAS) when associated with ASD and other rheumatic disorders. Typically, it will present as high-grade fever, new hepatosplenomegaly, lymphadenopathy, pancytopenia or bicytopenia (including low platelet counts) and abnormal liver enzymes; some patients can develop neurologic disturbances and bleeding disorder. Similar to ASD, markedly elevated ferritin level is also present. [12] Diagnosis should be suspected with changes in the clinical course of a patient with active rheumatic disease. Bone marrow biopsy will not always show the presence of hemophagocytes, especially if obtained early in the disease presentation. Imaging in early phases of ASD is generally non-contributive in establishing a diagnosis. Radionuclide bone scan and gadolinium-enhanced magnetic resonance imaging might be more sensitive imaging for early diagnosis and successful treatment in follow up. A study comparing the imaging of patients with ASD, juvenile arthritis and adult-onset rheumatoid arthritis revealed pericapitate articular alterations without radiocarpal involvement to be frequent in the setting of ASD.[13] An unusual complication of ASD is the rapid destruction of the hip and, less commonly, the knee, which can require total joint arthroplasty. [14] Our patient met all four major and four minor criteria; she had persistent high fever, severe sore throat, lymphadenopathy, and leukocytosis with elevated ESR. She had an evanescent rash and transaminitis at some point during the clinical course. Laboratory was not suggestive of HLH and
serology, septic work up and bone marrow biopsy excluded other diagnoses. The mainstay management of ASD is supportive, with fluids and antiinflammatory medications. In general, NSAIDs are to be tried first, but studies show that it provides remission and disease control in only 21% of patients. [15] Multiple studies reveal that corticosteroids are effective in controlling the disease by up to 60%. [6,7,15,16]. Addition of steroidsparing agents early in the course of the disease, in a patient that has not completely responded to steroids can decrease side effects and the dependence of steroids. Multiple disease modifying anti-rheumatic drugs have been studied in the management of ASD; methotrexate is the first line steroid-sparing treatment that can potentially prevent worsening of arthritis. During treatment with steroids, ESR, CRP and glycosylated ferritin levels should be checked to monitor response; some patients who initially shows a response can develop splenomegaly, persistently elevated ESR and low glycosylated ferritin which suggest consideration to use steroids sparing agents. [17] In a French study of 20 patients with ADS requiring ICU care, corticosteroids were given as the first line, with an efficacy of 50%. Anakinra, a biologic drug that helps to decrease inflammation in rheumatoid arthritis and other inflammatory diseases proved to be the most successful by being effective in 80% of the patients with ADS. [18] Immunosuppressants and biologic agents have been studied and proven effective in the maintenance phase of the disease. Patients with ASD can have elevated levels of cytokines such as interleukin (IL)-1, IL-6, interferon (IFN)-gamma, and tumor necrosis factor-alpha which are thought to be involved in the pathogenesis of the disease. Azathioprine, cyclosporine A, cyclophosphamide and leflunomide have proven efficacious as corticosteroid-sparing drugs in patients with multiple joint affected course of the disease.[19] Interleukin 1 (IL-1) antagonists have been used as third-line treatment (after corticosteroids and immunosuppressants have failed or had severe side effects) with promising results. Anakinra has been the main drug studied and proved to be not only effective in about 80% of the cases, but also has provided remission of disease after 3 months of use.[20] In the setting of IL-6 antagonists, Tocilizumab has been studied as a single agent in corticosteroid and methotrexate refractory ASD. Treatment duration was for 12 months and patients were observed for 18 months; resolution of fever and joint manifestations as well as decrease in ESR, CRP and ferritin levels, was observed with continued use of medication, making it a promising alternative to refractory disease.[21] Outcomes of patients with ASD falls in three possible courses of the disease: self-limited, intermittent flares and chronic disease, with about one-third falling in each category. Most of the patients with self-limited disease achieve remission in about 9 months. Patients with the intermittent disease develop recurrent episodes of flares with complete remission of symptoms between flares. Those with the chronic disease develop progressively worsening joint destruction.[22] In conclusion, patients presenting with adult onset of Still’s disease represent a challenge to the clinicians. A wide range of clinical presentation and severity of illness can be seen across all medical services, ranging from ambulatory setting to critical care. It is of the utmost importance to keep in mind the existence of this rare disorder, exclude other common and deadly conditions rapidly and ideally start early antiinflammatory treatment to avoid poor outcomes.
The authors have no conflict of interest to declare
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
